Endothelin-A receptors mediate vascular smooth-muscle response to moderate acidosis in the canine tibial nutrient artery

B. C. Coessens, V. M. Miller, M. B. Wood

Research output: Contribution to journalArticlepeer-review

4 Scopus citations

Abstract

Perfusate pH may influence the tone of vascular smooth muscle by affecting the release of endothelium-derived vasoactive factors or by directly modulating function of the smooth muscle. This study was designed to investigate the role of endothelium-derived factors on acidosis-induced responses of isolated canine tibial nutrient artery suspended in an organ chamber for the measurement of isometric contractile force. To investigate the specific role of the endothelium in half the rings, the endothelium was removed mechanically. Concentration response curves to KCl were obtained in the absence or presence of inhibition of two important endothelium-derived relaxing factors, nitric oxide and prostacyclin, and an inhibitor of receptors for the endothelium derived contracting factor, endothelin-1. Acidification of the perfusate from pH 7.45 to 7.0 significantly attenuated the contractions to KCl in arterial rings with endothelium (the mean of the effective concentration causing 50% of the maximal response for KCl at pH 7.45 and 7.0 was 12.31 ± 0.40 nM and 14.60 ± 0.55 nM, respectively). This difference was abolished by mechanical removal of the endothelium. In rings with endothelium, inhibition of nitric oxide or prostacyclin did not abolish the attenuation of KCl-induced contractions occurring with acidosis (the mean of the effective concentration causing 50% of the maximal response for KCl at pH 7.45 and 7.0 was 11.18 ± 0.60 nM and 13.60 ± 0.60 nM, respectively). Inhibition of endothelin-A receptors did not alter contractions to KCl at pH 7.45. However, the acidosis-induced attenuation of contractions with KCl was abolished by the endothelin A-receptor antagonist BO-123 (the mean of the effective concentration causing 50% of the maximal response at pit 7.45 and 7.0 was 13.8 ± 1.34 nM and 13.2 ± 1.34 nM, respectively). These results suggest that acidosis-induced relaxation of canine tibial nutrient artery is endothelium dependent and that activation of endothelin-A receptors during acidosis is coupled to a release of an endothelium-derived relaxing factor.

Original languageEnglish (US)
Pages (from-to)818-822
Number of pages5
JournalJournal of Orthopaedic Research
Volume14
Issue number5
DOIs
StatePublished - Sep 1996

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine

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